Decreased reproductive performance in xCT-knockout male mice

Abstract

Sulphoxidation occurs in protamines that are enriched in cysteine and supplies chromatin for packaging. The extracellular fluid contains higher levels of oxidised cysteine (cystine), and some cells utilise system x, a cystine transporter in which xCT is the main protein component, to fulfil the need for cysteine. We hypothesised that system x might ensure the supply of cysteine needed for spermatogenesis. The reproductive ability of xCT male mice at 6- to 18-weeks of age appeared to be lower than xCT male mice. The courtship behaviour of the xCT male mice was undynamic, which appeared to be associated with the low reproductive ability of xCT male mice. xCT was found to be expressed in mouse testes, notably in Sertoli cells, as well as in the epididymis and the levels were increased at the time of sexual maturation. Despite the normal histological appearance of testicular tissues, the cauda epididymis of xCT mice contained round, greater numbers of immature spermatogenic cells than that of xCT mice. However, there were no significant differences in the numbers of sperm stored in the cauda epididymis or in the concentrations of cysteine or glutathione in the testes. The resulting sperm had normal fertilising ability. Thus, system x appears to function as a backup system for supplying cysteine to testes and play a pivotal role in supplying cysteine for normal sexual behaviour by a mechanism that is different from that for the supply of cysteine in spermatogenesis.

The Stallion Spermatozoa: A Valuable Model to Help Understand the Interplay Between Metabolism and Redox (De)regulation in Sperm Cells

“…It is interesting that spermatozoa is one of the few cells constitutively expressing the SLC7A11 along with thymus, spleen and brain (33); mRNA is present in testis and the SLC7A11 knock out mouse display subfertility (67). The SLC7A11 is upregulated in many cancer cell lines (14,80), interestingly, and as seems to occur as well in the spermatozoa, high expression of the SLC7A11 in cells, is linked to high activity of the PPP (90), with cells expressing high amounts of this protein expressing also high amounts of enzymes involved in the PPP, particularly G6PD.…”

The incorporation of cystine by the soluble carrier family 7 member 11 (SLC7A11) is a component of the redox regulatory mechanism in stallion spermatozoa†

“…The availability of cysteine/cystine is the rate-limiting step in GSH synthesis, with cysteine incorporated via the Na+-dependent Alanine-Serine-Cysteine (ASC) group or transporters such as ACS1 (SLC7A10) [17][18][19][20] and cystine incorporated via the soluble family 7 carrier member 11 (SLC7A11) antiporter, the Na+-independent exchange system for cystine/glutamate [18]. SLC7A11 is constitutively expressed in a limited number of organs, such as the thymus, spleen and brain [21], but SLC7A11 mRNA is expressed in testis and SLC7A11 knockout male mice display reduced reproductive performance [22]. Moreover, cysteine is also synthetized from methionine by the enzymes cystathionine beta-synthase (CBS) and cystathionase.…”

Dietary Cystine Ameliorates Defects in Spermatogenesis via Testosterone Production Induced by Protein Deficiency and Darkness in Rats

“…It is reported that cys- tine addition to casein-based low protein diet increases plasma cystine about two-fold (18). In a low protein diet, testicular cystine may be reduced from normal amount (19), which would be necessary to produce cysteine-rich protein, protamine that packages chromatin into sperm head (20). Under the normal lighting condition, cystine addition to low protein diet did not increase plasma testosterone (9PC) nor the rhythm.…”